Zenocutuzumab‑zbco Receives FDA Orphan Drug Designation for Treatment of Cholangiocarcinoma

Designation strengthens BIZENGRI® development program in rare cholangiocarcinoma

LEXINGTON, Mass., Feb. 5, 2026 /PRNewswire/ — Partner Therapeutics, Inc. (PTx), a privately held, fully integrated biotechnology company, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to zenocutuzumab‑zbco for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma. Zenocutuzumab-zbco is being developed in a subset of patients with cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion.

Cholangiocarcinoma (CCA) is a rare, aggressive malignancy of the bile ducts, typically diagnosed at an advanced stage when curative options are limited. There are approximately 8,000 cases annually in the United States, and the five-year survival rate for all stages remains below 15 percent, emphasizing the need for new therapeutic approaches. NRG1 gene fusions result from structural DNA rearrangements and typically occur without other oncogenic alterations. Like other fusions, they are best detected with a combination of tissue-based RNA and DNA next generation sequencing.

Systemic first-line treatment regimens in cholangiocarcinoma yield modest clinical benefit, with overall response rates (ORRs) of 26% to 29% and median overall survival (OS) of 11.7 to 12.8 months. Second-line treatment with FOLFOX provides an ORR of 5%, progression free survival of 4.0 months, and median OS of 6.2 months. Zenocutuzumab-zbco has shown activity in patients with cholangiocarcinoma harboring NRG1 gene fusion.

“Patients with cholangiocarcinoma face a particularly aggressive cancer with poor prognosis and limited treatment options. Receiving Orphan Drug Designation for zenocutuzumab in patients with CCA harboring the NRG1 gene fusion is a significant regulatory milestone for Partner Therapeutics and highlights the urgent need for new and effective treatment options for patients with this disease” said Juan W. Valle, MD, Chief Medical Officer of the Cholangiocarcinoma Foundation.

The FDA grants Orphan Drug Designation to investigational products designed to treat rare diseases or conditions affecting fewer than 200,000 people in the United States. Designation benefits may include up to seven years of market exclusivity upon approval, exemption from FDA user fees, eligibility for clinical‑trial tax credits, and closer collaboration with the Agency during development.

Zenocutuzumab‑zbco, marketed as BIZENGRI®, received Breakthrough Therapy Designation from the FDA in October 2025 and was granted accelerated approval in December 2024 for adults with advanced unresectable or metastatic non‑small cell lung cancer and pancreatic ductal adenocarcinoma harboring NRG1 gene fusions following prior therapy.

For more information on the eNRGy trial and zenocutuzumab-zbco, please visit www.partnertx.com.

About NRG1 Gene Fusions

NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activate downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. Comprehensive molecular testing, notably the combination of tissue-based DNA and RNA next generation sequencing, is essential to identify rare and actionable gene fusions, including NRG1.

About BIZENGRI (zenocutuzumab-zbco)

INDICATIONS

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 

Important Safety Information

BOXED WARNING: EMBRYO-FETAL TOXICITY

Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.

WARNINGS AND PRECUATIONS

Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions

BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.

In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion.

Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions. 

Interstitial Lung Disease/Pneumonitis

BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis.

In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated.

Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed. 

Left Ventricular Dysfunction

BIZENGRI can cause left ventricular dysfunction.

Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.

In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event.

Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI. 

Embryo-Fetal Toxicity

Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In post marketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose. 

ADVERSE REACTIONS

NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC

Serious adverse reactions occurred in 25% of patients with NRG1 gene fusion positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each).

In patients with NRG1 gene fusion positive NSCLC who received BIZENGRI, the most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%), diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%).

NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma

Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI.

There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure.

In patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%), musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%). 

Please see full Prescribing Information, including Boxed Warning

About Partner Therapeutics

Partner Therapeutics, Inc. (PTx), an integrated biotechnology company, focuses on development and commercialization of therapeutics to improve health outcomes in cancer and serious diseases, as well as global health security threats. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. PTx’s portfolio includes zenocutuzumab-zbco (BIZENGRI®) and sargramostim (EU: IMREPLYS®; US: LEUKINE®; and with Nobelpharma Co. Ltd for JAPAN: SARGMALIN®). Visit www.partnertx.com.

References:

1. BIZENGRI (zenocutuzumab-zbco) injection [package insert]. Available at: https://www.bizengrihcp.com/pi
2. American Cancer Society (ACS). Key statistics about bile duct cancer. Last Revised: October 11, 2024. Accessed at https://www.cancer.org/cancer/types/bile-duct-cancer/about/key-statistics.html, on 25 Jul 2025.
3. Schram AM, Goto K, Kim DW, et al. Efficacy of zenocutuzumab in NRG1 fusion–positive cancer. N Engl J Med. 2025;392:566-76. doi: 10.1056/NEJMoa2405008
4. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-81. doi:10.1056/NEJMoa0908721
5. Oh DY, Ruth He A, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8):EVIDoa2200015. doi:10.1056/EVIDoa2200015
6. Kelley RK, Ueno M, Yoo C, et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet.2023;401(10391):1853-65. doi:10.1016/s0140-6736(23)00727-4. Erratum in: Lancet. 2024 Mar 23;403(10432):1140. doi: 10.1016/S0140-6736(24)00545-2.

BIZENGRI^® is a registered trademark of Merus B.V. Under an agreement with Merus, PTx has exclusive rights to develop, manufacture, and commercialize zenocutuzumab-zbco for the treatment of NRG1+ cancer in the U.S. and provide the product on a named-patient basis for this use outside of the U.S. pending future regulatory developments.

PARTNER THERAPEUTICS^®, IMREPLYS^®, and LEUKINE^® are registered trademarks owned by Partner Therapeutics, Inc. ©2026 Partner Therapeutics, All rights reserved.

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SOURCE Partner Therapeutics, Inc.